HCV infection increases the risk of diabetes in individuals with metabolic syndrome, and may worsen glycemic control in those with diabetes, according to Dr. George Ioannou of the University of Washington, Seattle, and colleagues. To see whether clearing the virus with DAAs has an impact, the team reviewed data from 2,435 patients with diabetes (97% men, mean age 62, about 40% white/40% black) who underwent DAA-based antiviral treatment (no interferon or ribavirin) for HCV in the U.S. Veterans Affairs health care system in 2014 and 2015.

The team compared changes in average hemoglobin A1c (HbA1c) levels and use of antidiabetic medications the year before and after antiviral treatment between patients who achieved a sustained virologic response (SVR) - defined as a viral load below the lower limit of quantification 12 weeks or more after the end of treatment - and those who did not.

Almost all (99%) participants had genotype 1 HCV, and were treated with LDV/SOF (ledipasvir/sofosbuvir; 56.2%) or SMV (simeprevir) plus SOF (38.3%).

As reported online June 28 in Diabetes Care, 2,180 patients achieved an SVR and 255 did not.

Compared with those whose HCV treatment failed, patients who achieved an SVR were less likely at baseline to have cirrhosis (35.3% versus 54.5%) and decompensated cirrhosis (9.3% versus 20%).

They were also less likely to be taking antidiabetic medications (74.8% versus 78.0%) or insulin (41.3% versus 49.8%).

Among those with elevated baseline HbA1c, DAA treatment was associated with a greater HbA1c reduction in patients who achieved SVR (0.98%) than in those who did not (0.65%; adjusted mean difference 0.34, P = 0.02).

Use of antidiabetic medications decreased more in patients who achieved SVR than in those who did not, especially insulin use, which dropped significantly to 38% in patients achieving SVR compared with a slight increase to 51% in those who sustained treatment failure.

Comparing the pre- and post-treatment periods, weight increased slightly more in patients with an SVR than in those whose treatment failed. Hemoglobin concentrations decreased significantly more in patients whose treatment failed than in those who achieved an SVR.

Serum creatinine levels increased slightly and similarly in patients who did and did not achieve an SVR.

After adjusting for changes in weight, hemoglobin concentrations, and creatinine, the associations between SVR and an HbA1c drop or antidiabetic medication use remained essentially unchanged.

Summing up, Dr. Ioannou told Reuters Health by email, “After treatment of HCV with DAAs in diabetic patients, there appeared to be an improvement in glycemic control as demonstrated by decreased HbA1c levels and decreased number of insulin prescriptions. I believe our study does suggest an endocrine benefit to viral eradication and thus could be an additional compelling reason to treat chronic hepatitis C in diabetic patients.”

Dr. Valentina Rodriguez, an endocrinologist at NYU Langone Medical Center in New York City, told Reuters Health, “It is exciting to have new data which not only confirms the previously studied association between type 2 diabetes and HCV, but also demonstrates beneficial effects of newer DAAs on improvement in A1C and reduction in insulin requirements.”

The researchers did “a good job” of controlling for confounders such as weight loss, which might have accounted for the glycemic control benefits seen with interferon, she noted by email.

“Importantly,” she added, “the study also accounted for other variables that could have falsely lowered/raised hemoglobin A1C testing in patients with treated/untreated HCV, including anemia and chronic kidney disease. This makes the interpretation of improved glycemic control more reliable.”

“Some caveats we should keep in mind are the follow-up time for this study; though it is encouraging that insulin requirements and A1C decreased in the first 15 months post-therapy, longer term data with regards to micro/macrovascular complications (are) unavailable,” Dr. Rodriguez continued.

“Also, not all HCV genotypes were studied; patients with HCV genotypes 2 and 3 were not included, possibly because they have been shown to be notably less cost-effective to treat with DAA therapy than the genotype 1 patients,” she observed.

“The practical implementation of newer, more expensive drugs such as DAAs can be challenging,” she acknowledged. “However, when considering that the price of insulin has increased by over 200% over the last four years, we must readdress the cost effectiveness of these drugs for patients with both type-2 diabetes and HCV.”

Dr. Rodriguez concluded, “Future studies with longer follow up times will be helpful in establishing whether treatment of HCV with DAAs will also lead to decreased cardiovascular events and other diabetes-related deaths, which would impact healthcare spending even more significantly.”